The goal of this project is to identify how aging affects neuronal and neuromuscular function. These studies are being performed using the nematode, C. elegans, which offers both genetic and cell biological approaches for studying this problem. In C. elegans, aging affects locomotory ability much more dramatically than sensory ability, which is relatively well-maintained during aging. The basis for this age-related locomotory deficit may be due to structural decline of the muscles or to impaired signaling at the neuromuscular junction. Both pharmacological and structural studies of aging neurons and muscles are being employed to investigate these possibilities. In addition, a genetic screen was conducted to identify genes that are required for normal age-related locomotory decline. This screen identified three mutants that appear to progress through aging faster than wild-type animals and one mutant that may be slowed in the progression of aging. Molecular identification of the genes mutated in these animals with accelerated or delayed-aging phenotypes will improve the understanding of the basis for age-related declines in movement and nervous system fuction.